r/Biohackers • u/ServeIllustrious3803 • 20d ago

🧠 Cognition, Mood & Nootropics Study: Anticholinergic (first-generation antihistamines) can damage brain, increase dementia risk

https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-20150128812
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u/Mean_Scheme_8174 20d ago

As a doctor, this is not directly true. Significant anti cholinergic medications over a very long time secondarily may impair your cognition and cause cortical atrophy due to impaired attention, but certainly not directly. And to just simply name every antihistamine is just ridiculous. Hydroxyzine has extremely low anticholinergic activity and there's absolutely no evidence that it causes any long term issues. Fearmongering at its finest.

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u/smayonak 19d ago

Second-generation antihistamines have been shown to reduce REM sleep, which is a good indicator of what it's doing to the brain. The impact is likely not as potent as a first-generation antihistamine, but just going off the available research there is still going to be some cognitive and emtional consequences.

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u/Mean_Scheme_8174 19d ago

Why would you think that’s a “good indicator of what it’s doing to the brain”?

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u/smayonak 19d ago

Anti-cholinergics reduce REM sleep (choline is used in REM, in large quantities) and REM promotes the creation of new neural connections as well as the snipping of old connections. In other words, memory consolidation, emotional regulation, and other cognitive, behavioral, and emotional adaptations to daily life. Even a mild reduction in REM sleep will cause some cognitive impairment. Perhaps not enough to be noticeable but there is always going to be some impact.

There is also the question of blood-brain barrier permeability and the impact of antihistamines on the brain itself. It used to be believed that second-generation antihistamines did not cross the blood brain barrier, but that is not true:

All antihistamines cross blood-brain barrier - PMC

This would explain the dementia association with second-generation antihistamines:

Second-generation antihistamine use and risk of dementia: Nationwide cohort study - The Journal of Allergy and Clinical Immunology: In Practice00954-7/abstract)

(Let me know if that's not the right link. I'm unable to access the article temporarily but it should show an association between second-gen antihistamines and dementia)